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David S. Ettinger, MD, FACP, FCCP

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SITC 2022: Immunity Hubs and Response to Immunotherapy in NSCLC

By: Kayci Reyer
Posted: Thursday, December 1, 2022

According to research presented at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 956), spatially clustered immunity hubs found within immunogenic tumors may be prognostic indicators of response to immunotherapy in patients with non–small cell lung cancer (NSCLC). The immunity hubs may also be responsible for creating a looped environment that may stimulate additional T-cell activity. Some immunity hubs, called hybrid hubs, were found to overlap with CD8 T-cell sites.

“Moreover, hybrid hubs may represent an active intratumoral niche for tumor-specific stem-like T cells that sustain antitumor immunity,” concluded Jonathan Chen, MD, PhD, of Massachusetts General Hospital, Boston, and colleagues. “These multicellular networks are excellent candidates for biomarker development and targets for immunotherapy.”

The study included tumor tissue from 68 patients with NSCLC who had not yet received PD-1 blockade. The samples underwent multiplex RNA fluorescence in situ hybridization to identify immunity hubs and their components. The presence of immunity hubs was associated with response to PD-1 blockade. According to the investigators, immunity hubs were found to generate antitumor T-cell activity and to contain CD8 T cells in various states.

Patients who experienced a response had immunity hubs with a higher concentration of activated CD8 T cells and interferon gamma–positive cells than those who did not experience a response. Hybrid hubs, which were identified when hubs were subcategorized by phenotype, shared characteristics with the interfollicular zone of lymph nodes. A strong correlation was noted between the presence of a hybrid hub and RECIST response (P = .0005). A total of 85% of patients who experienced a response also had a hybrid hub, whereas 24% of patients who did not experience a response harbored a hybrid hub. The presence of hybrid hubs was also associated with progression-free survival outcomes (P = .0014).

Disclosure: No disclosure information was provided.


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